Inflammatory or degenerative condition of the musculoskeletal system, such as arthrosis, osteoarthritis, rheumatic joint disease, joint stiffness, pain in connection with muscles, joints and surrounding tissues or the skeleton, and swelling in connection with muscles or joints and surrounding tissues, are painful and frequent medical conditions, in particular, in the elderly.
In particular, osteoarthritis (OA), the most common form of joint disease, affects as much as 80% of the general population. The degenerative joint changes that characterize this disorder are radiologically detectable and include subchondral bony sclerosis, synovitis, loss of articular cartilage, and osteophytes formed by proliferation of bone and cartilage in the joint Altman 1986, Arthritis Rheum 29: 1039-1049). In about 60% of sufferers these changes are accompanied by symptoms that include erythema, swelling and joint pain that often result in reports of morning stiffness, limitations in range of motion and restrictions in the activities of daily living (Fries 1980, Arthritis Rheum 23: 137-145).
The Framingham Osteoarthritis study demonstrated that radiographic evidence of OA increased with age, from 27% in patients younger than age 70, to 44% in patients age 80 or older. There was a slightly higher prevalence of radiographic changes of OA in women than in men (34% versus 31%); however, there was a significantly higher proportion of women with symptomatic disease (11% of all women versus 7% of all men; p=0.003) (Felson 1987, Arthritis Rhem 30(8): 914-918).
Pharmacological treatments for OA include analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), intra-articular (IA) injections of steroids and IA injections of viscosupplementation in the form of hyaluronic acid (HA) (Kirchner 2006. Osteoarthritis Catilage 14(2): 154-62). Several retrospective analyses have concluded that non-selective NSAIDs pose an increased risk of gastrointestinal adverse events (AEs) (see, e.g., Laine 2006, J Cardiovasc Pharmacol 47 Suppl 1, 60-66) In general, these analyses have looked at patients undergoing long-term chronic therapy often with underlying inflammatory diseases such as OA. Intra-articular injection of steroid is also a common treatment for osteoarthritis of the knee. However, clinical evidence suggests that the benefit is short-lived, usually one to four weeks (Bruce 2004, BMJ, doi:10.1136/bmj.38039.573970.7C). Additionally, concern has been expressed that long-term treatment could promote joint destruction and tissue atrophy.
The data from clinical trials of viscosupplement products available in the public domain utilized heterogeneous methodologies and endpoints, and comparisons are therefore relatively difficult to interpret. These products appear to provide, at best, consistently moderate symptom improvement of OA knee pain despite the fact that viscosupplementation is universally used at a very significant cost. Improvements are often directional, and even when statistically significant, may not exhibit clinical endpoint effect sizes consistent with clinically relevant outcomes. It has, in fact, been concluded in a systematic review of the literature that IA HA has not been proven clinically effective and may be associated with a greater risk of AEs (Rutjes 2012, Ann Intern Med 157(3): 180-191).
In light of the increasing prevalence of OA in a large and aging “baby-boomer” population in the United States, there is a clear public health need for new OA treatment approaches that do not present potentially harmful outcomes.
Two homeopathic drugs have been suggested for therapy of conditions of the skeletal and muscle system.
Traumeel® Injection Solution (Traumeel® injection) is a marketed anti-inflammatory, anti-edematous, anti-exudative combination formulation of 12 botanical substances and 2 mineral substances. Traumeel® injection is officially classified as a homeopathic combination medication (Homeopatic Pharmacopeias Europe (Ph Eur) and US (HPUS)). Botanical ingredients are Arnica montana radix (mountain arnica), Calendula officinalis (marigold), Hamamelis virginiana (witch hazel), Millefolium (milfoil), Belladonna (deadly nightshade), Aconitum napellus (monkshood), Chamomilla (chamomile), Symphytum officinale (comfrey), Bellis perennis (daisy), Echinacea angustifolia (narrowleafed cone flower). Echinacea purpurea (purple cone flower), and Hypericum perforatum (St. John's wort). The mineral ingredients are Hepar sulphuris calcareum (calcium sulfide) and Mercurius solubilis Hahnemanni (Dimercuros ammonium nitrate). The ingredients are decimal attenuations of different potencies as per the Homeopathic Pharmacopoeia of the United States (HPUS).
Traumeel® is a multicomponent and multitargeting complex homeopathic medication. The exact mechanism of action of Traumeel® has not been fully elucidated. However, in vitro and animal studies point to a multi-targeted mechanism of action.
Various cellular and biochemical pathways appear to be modulated by the ingredients of Traumeel®, which act synergistically on the different phases of the inflammatory response (Lussignoli 1999, Complement Ther Med 7: 225-230). However, Traumeel® injection does not inhibit the arachidonic acid pathway of prostaglandin synthesis. Traumeel® appears to reduce acute local inflammation without affecting the normal defensive and homeostatic functions of granulocytes or platelets, and to regulate the orchestration of the overall acute local inflammatory process instead of interacting with a specific cell type or biochemical mechanism (Conforti 1997, Biomed ther 15: 28-31). Preclinical studies suggest Traumeel® inhibits the secretion of pro-inflammatory mediators, and regulates lymphocytes and their messengers (e.g. transforming growth factor-beta, tumour necrosis factor-alpha and interleukin-1 (Porozov 2004, Clin Dev Immunol 2: 143-9; Heine 2002, Ärztezeitschrift für Naturheilverfahren 43: 96-104; Heine 1998, Biomed Ther XVI: 224-6). Traumeel® also seems to act by accelerating the healing process rather than blocking edema development from the start, with beneficial effects on tissue repair and wound healing (Lussignoli 1990, loc. cit., Conforti 1997, loc. cit., Heine 1998, loc. cit., Heine 2002, loc. cit., Schneider 2008, Complement Ther Med 16-22-7). Lastly in recent genomic studies, Traumeel® has been seen to have beneficial effects on the inflammatory process in a wound healing model (St. Laurent, G., M. Tackett, T. McCaffrey, P. Kapranov. DEEP SEQUENCING TRANSCRIPTOME ANALYSIS OF TRAUMEEL THERAPEUTIC ACTION IN WOUND HEALING. Annals of the Rheumatic Diseases; Vol 72: Suppl 3 [Abstract THU0016] (2013)).
Zeel® injection solution is officially classified as a homeopathic combination medication (Homeopatic Pharmacopeias Europe (Ph Eur) and US (HPUS)). Botanical or animal ingredients are Arnica montana, radix, Cartilago suis (porcine cartilage), Coenzyme A, Solanum dulcamara (bittersweet), Embryo totalis suis (porcine embryo), Funiculus umbilicalis suis (porcine umbilical cord), Placenta suis (porcine placenta), Rhus toxicodendron (poison oak), Sanguinaria Canadensis (blood root), Symphytum officinale cornfrey). The mineral ingredients are Natrum oxalaceticum (di-sodium oxaloacetate), Nadidum (beta-NAD), a-Lipoicum acidum (thioctic acid), and Sulphur (sulfur). The ingredients are decimal attenuations of different potencies as per the Homeopathic Pharmacopoeia of the United States (HPUS).
Zeel® has been shown to modulate chronic inflammatory processes by inhibiting the production of leukotriene B4 by 5-lipoxygenase and Traumeel® the synthesis of prostaglandin E2 by cyclooxygenase (COX)-1 and COX-2 enzymes (Jäggi 2004, Inflamm Res 53(4): 150-7; Tunon 1995, J Enteropharmacol 48: 61-76). Zeel® injections have also demonstrated several different roles in preserving cartilage. It appears to act as an anti-angiogenic agent by preventing vascularisation of cartilage and endochondrium, and stimulates the release of transforming growth factor-beta, which is involved in immunomodulation and tissue remodeling (Basini 2007, Biofactors 29(1): 11-18; Basini 2007, Ann N Y Acad Sci 1095: 371-6; Schmolz 2000, Biol Med 29(1): 31-34; Schmolz 2001, Biol Med 30(2): 61-65). Additionally, Zeel® significantly decreases the severity of cartilage damage, and improves the mechanical properties of osteoarthritic cartilage by increasing its elasticity (Stancikova 1999, Rheumatologia 13(3): 101-108; Weh 1990, Biol Ther 8(4): 91-93).
However, improved therapies for OA and other inflammatory or degenerative conditions of the musculoskeletal system are not yet available but still highly desired.